Altered regulatory T-cell fractions and Helios expression in clinically isolated syndrome: clues to the development of multiple sclerosis

Development of multiple sclerosis (MS) is frequently preceded by an acute or subacute neurological disturbance referred to as clinically isolated syndrome (CIS). The specific immunological disturbances present in CIS remain underexamined. This study analysed peripheral blood mononuclear cells from n = 18 treatment-naive individuals with recently diagnosed CIS (o120 days) for disturbances in the phenotype of T regulatory (Treg), follicular T regulatory (Tfr), T helper (Th), follicular T helper (Tfh) and B cells. Relative to healthy controls (n = 19), CIS was associated with lower proportions of suppressive CD45RA^þ FoxP3^lo Treg and Tfr cells and greater proportions of non-suppressive CD45RA FoxP3^lo and Th17-like Treg and Tfr. Lower Helios expression (mean fluorescence intensity) was measured across all Treg and Tfr fractions in the CIS group, suggesting less potent regulatory function. Greater frequencies of activated, efficient B-cell helper Tfh subsets and a trend for a higher proportion of IgD⁻ CD27⁻ B cells was also detected in the CIS group, characteristics that were positively correlated with Treg and Tfr Helios expression. These results indicate that Treg and Tfr impairment is an early feature in MS.